COMP与PBM化疗方案治疗晚期鼻咽癌的疗效分析

我们以ＣＴＸ＋ＶＣＲ＋ＭＴＸ＋ＤＤＰ（ＣＯＭＰ）和ＤＤＰ＋ＢＬＭ＋ＭＴＸ（ＰＢＭ）两种化疗方案治疗复发和转移的晚期鼻咽癌５８例，４９例可评价客观疗效。结果ＣＯＭＰ组取得了ＣＲ３例，ＰＲ９例，有效率（ＣＲ＋ＰＲ）为５２．２％；ＰＢＭ组ＣＲ１例，ＰＲ９例，有效率（ＣＲ＋ＰＲ）为３８．５％。两者无显著性差异（Ｐ〉０．０５）。治疗后有效病例缓解期为５～５６月，中位缓解期为２５月。两种方案对鼻咽癌肺转移均较     

结直肠癌ＣＯＸ-２蛋白表达水平及其与临床关系的Ｍｅｔａ分析

目的　系统评价环氧化酶 ２（ＣＯＸ ２）在结直肠癌中表达水平及其与临床病理特征的关系。方法　计算机检索ＣｏｃｈｒａｎｅＬｉｂｒａｒｙ、ＰｕｂＭｅｄ、ＣＮＫＩ等数据库,按照纳入与排除标准选择研究文献,评价质量及提取资料后采用Ｓｔａｔａ１１.０软件对数据库进行系统评价。结果　共纳入１４项研究,其中结直肠癌患者１２００例,正常对照２７６例。Ｍｅｔａ分析结果显示：（１）ＣＯＸ-２在结直肠癌组及正常对照组中的表达差异有统计学意义（ＯＲ＝２４.４９,９５％ＣＩ＝１５.９５～３７.６０,Ｐ＝０.０００）;（２）ＣＯＸ-２表达水平与结直肠癌临床病理特征的关系为：男性与女性（ＯＲ＝１.７７,９５％ＣＩ＝０.７９～３.９４,Ｐ＝０.１６５）,年龄＜５０岁与≥５０岁（ＯＲ＝０.５２,９５％ＣＩ＝０.２４～１.１１,Ｐ＝０.０８９）,结肠癌与直肠癌（ＯＲ＝０.９８,９５％ＣＩ＝０.７０～１.３９,Ｐ＝０.９２４）,Ｔ１＋Ｔ２与Ｔ３＋Ｔ４（ＯＲ＝２.３７,９５％ＣＩ＝０.９６～５.８９,Ｐ＝０.０６３）,肿瘤直径≥５ｃｍ与＜５ｃｍ（ＯＲ＝３.０７,９５％ＣＩ＝１.９４～４.８６,Ｐ＝０.０００）,淋巴结转移与无淋巴结转移（ＯＲ＝３.０８,９５％ＣＩ＝１.７３～５.４８,Ｐ＝０.０００）,Ｄｕｋｅｓ分期中Ｃ＋Ｄ期与Ａ＋Ｂ期（ＯＲ＝３.０８,９５％ＣＩ＝１.２５～７.６１,Ｐ＝０.００２）,低分化与高、中分化（ＯＲ＝１.７０,９５％ＣＩ＝１.０６～２.７３,Ｐ＝０.０２７）。结论　ＣＯＸ-２在结直肠癌中表达增高,且其高表达增加了结直肠癌恶性行为发生的危险。     

紫杉醇及塞来昔布对胃癌细胞株ＣＯＸ-２及Ｐ-ｇｐ表达的影响

目的：观察紫杉醇及环氧化酶-２（ＣＯＸ-２）选择性抑制剂塞来昔布（Ｃｅｌｅｃｏｘｉｂ）对人胃腺癌细胞株ＢＧＣ-８２３ ＣＯＸ-２及Ｐ-糖蛋白（Ｐ-ｇｐ）表达的影响,探讨ＣＯＸ-２在化疗药物诱发多药耐药（ＭＤＲ）产生机制中的作用。方法：采用ＭＴＴ法检测紫杉醇不同剂量、不同时间点及塞来昔布不同剂量对胃腺癌细胞株ＢＧＣ-８２３生长的影响,在此基础上采用Ｗｅｓｔｅｒｎｂｌｏｔ方法检测一定剂量范围内某一时间点的紫杉醇对ＢＧＣ-８２３ ＣＯＸ-２、Ｐ-ｇｐ表达的影响及联合塞来昔布后两种蛋白表达的变化。结果：紫杉醇对胃腺癌细胞株ＢＧＣ-８２３的生长为细胞毒作用,呈时间和剂量依赖性。在一定剂量范围内和某一时间点,随着紫杉醇剂量逐渐升高,ＢＧＣ-８２３的ＣＯＸ-２、Ｐ-ｇｐ表达均呈上升趋势;且这两种蛋白在联合塞来昔布应用后表达均呈下降趋势。结论：紫杉醇可诱导胃腺癌细胞株ＢＧＣ-８２３ ＣＯＸ-２及Ｐ-ｇｐ蛋白的表达,这种表达能被塞来昔布所抑制。ＣＯＸ-２表达的诱导在紫杉醇诱导的Ｐ-ｇｐ表达中起着重要作用。     

COMP和PBM化疗方案治疗晚期鼻咽癌的疗效分析

我们以ＣＴＸ＋ＶＣＲ＋ＭＴＸ＋ＤＤＰ（ＣＯＭＰ）和ＤＤＰ＋ＢＬＭ＋ＭＴＸ（ＰＢＭ）两种化疗方案治疗复发和转移的晚期鼻咽癌５８例。４９例可评价客观疗效。结果ＣＯＭＰ组取得ＣＲ３例、ＰＲ９例，有效率（ＣＲ＋ＰＲ）为５２．２％；ＰＢＭ组ＣＲ１例、ＰＲ９例，有效率（ＣＲ＋ＰＲ）为３８．５％。两者无显著性差异（Ｐ＞０．０５）．治疗后有效病例缓解期为５～５６月，中位缓解期为２５月。两种方案对鼻咽癌肺转移均较好，对肝转移疗效最差。ＣＯＭＰ方案对鼻咽癌远处转移疗效较好，对肺转移有效率为５８．３％（７／１２）．可作为鼻咽癌远处转移尤其是肺转移的首选。ＰＢＭ方案对鼻咽癌原灶复发疗效较好，对鼻咽癌复发有效率为４２．９％（３／７），可作为鼻咽癌原灶复发或放射治疗后辅助化疗首选方案。     

CHOP与CNOP治疗非何杰金氏淋巴瘤的对比观察报告

ＣＨＯＰ（ＣＴＸ、ＡＤＭ、ＶＣＲ、ＰＤＮ）联合化疗方案是治疗非何杰金氏淋巴瘤（Ｎｏｎ—Ｈｏｄｇｋｉｎ′ｓＬｙｍｐｈｏｍａＮＨＬ）常用的、有效的方法之一。米托蒽醌是一有效的、广谱的、细胞周期非特异性抗癌药，化学结构与阿霉素相似，抗癌活性与ＡＤＭ相当或略高，它无氨基糖结构，心脏毒性较ＡＤＭ低。对确诊为ＮＨＬ３６例住院患者，随机分为ＣＨＯＰ组和ＣＮＯＰ组各１８例作临床对比观察。ＣＨＯＰ组ＣＲ２例、ＰＲ７例，有效率５０％（９／１８）；ＣＮＯＰ组ＣＲ４例、ＰＲ７例，有效率６１．１％（１１／１８），两组疗效相似（Ｐ＞０．０５）。     

CHOP与CNOP治疗非何杰金氏淋巴瘤的对比观察报告

ＣＨＯＰ（ＣＴＸ、ＡＤＭ、ＶＣＲ、ＰＤＮ）联合化疗方案是治疗非何杰金氏淋巴瘤（Ｎｏｎ－Ｈｏｄｇｋｉｎ‘ｓ Ｌｙｍｐｈｏｍａ ＮＨＬ）常用的、有效的方法之一。米托蒽醌是一有效的、广谱的、细胞周期非特生抗癌药，化学结构与阿霉素相似，抗癌活性与ＡＤＭ相当或略高，它无氢基糖结构。心脏毒性罗ＡＤＭ低。对确诊断ＮＨＬ３６例住院患者，随机分为ＣＨＯＰ组和ＣＮＯＰ组各１８例作临床对比观察。ＣＨＯＰ组ＣＲ２例、ＰＲ     

SEARCH FOR HERPES SIMPLEX VIRUS TYPE2（HSV－2）AND HUMAN PAPILLOMAVIRUS（HPV）IN THE NORMAL AND ABNORMAL CERVICAL SAMPLES

ＳＥＡＲＣＨＦＯＲＨＥＲＰＥＳＳＩＭＰＬＥＸＶＩＲＵＳＴＹＰＥ２（ＨＳＶ－２）ＡＮＤＨＵＭＡＮＰＡＰＩＬＬＯＭＡＶＩＲＵＳ（ＨＰＶ）ＩＮＴＨＥＮＯＲＭＡＬＡＮＤＡＢＮＯＲＭＡＬＣＥＲＶＩＣＡＬＳＡＭＰＬＥＳＺｈａｎｇＷｅｉ;张伟;ＪｉｎＳｈｕｎｑｉａ...     

骨及软组织恶性肿瘤大剂量顺铂与甲氨喋呤化疗中肾损害的监测

对２１例骨及软组织恶性肿瘤病人手术前后给予４４次大剂量ＤＤＰ（１００ｍｇ／ｍ＾２），ＭＴＸ（２００ｍｇ／ｋｇ）化疗。化疗前后分别测定血清尿素（ＵＲＥＡ），血清肌酐（Ｃｒ），血和尿中β２－ＭＧ的含量，结果ＤＤＰ化疗组２０例病人有１４例中β２－ＭＧ含量升高（Ｐ〈０．０５）。作者认为用同位素方法测定尿中β２－ＭＧ值观察接受大量ＤＤＰ、ＭＴＸ化疗骨及软组织病人的肾功能损害程度，结果稳定可靠。化疗前尿中β２     

EXPRESSIONS OF ESTROGEN OCCUPIED RECEPTOR（EoR） AND PROGESTERONEOCCUPIED RECEPTOR（PoR） AND C－erbB－2ONCOPROTEININ HUMANNASOPHAR

ＥＸＰＲＥＳＳＩＯＮＳＯＦＥＳＴＲＯＧＥＮＯＣＣＵＰＩＥＤＲＥＣＥＰＴＯＲ（ＥｏＲ）ＡＮＤＰＲＯＧＥＳＴＥＲＯＮＥＯＣＣＵＰＩＥＤＲＥＣＥＰＴＯＲ（ＰｏＲ）ＡＮＤＣ－ｅｒｂＢ－２ＯＮＣＯＰＲＯＴＥＩＮＩＮＨＵＭＡＮＮＡＳＯＰＨＡＲＹＮＧＥＡＬＣＡＲＣ...     

鼻咽癌患者血清LHP、GSH－PX、SOD活性变化的临床意义

本文测定２４例鼻咽癌患者血清脂质过氧化氢（ＬＨＰ）、谷胱甘肽过氧酶（ＧＳＨ－ＰＸ）、超氧化物歧化酶（ＳＯＤ）（包括总超氧化物歧化酶Ｔ－ＳＯＤ、锰超氧化物歧化酶Ｍｕ－ＳＯＤ，铜锌超氧化物歧化酶Ｃｕ，Ｚｎ－ＳＯＤ）变化、结果ＬＨＰ增高明显，与对照组相比（Ｐ＜０．０１）。表明鼻咽癌与氧自由基（ＯＦＲ）损伤有关。ＧＳＨ－ＰＸ，Ｔ－ＳＯＤ，Ｍｕ－ＳＯＤ降低明显，与对照组相比（Ｐ＜０．０１）。说明鼻咽癌患者存在着ＯＦＲ清除酶系统障碍。揭示对ＬＨＰ，ＧＳＨ－ＰＸ，ＳＯＤ检测有助于鼻咽癌的诊断、病情判断及愈后评价，在鼻咽癌放、化疗中，运用自由基清除剂，有可能提高临床疗效。     

化疗药物致手足综合征防治研究进展

目的:总结分析化疗药物致手足综合征(HFS)的发病机制及对其采取的相关防治措施。方法:以"手足综合征、化疗药物和毒副反应"为关键词,计算机检索PubMed及CNKI数据库,检索年限为1996-2007年,选择标准:1)HFS的发生与化疗有关;2)HFS的预防及治疗。共筛选符合文献45篇。结果:HFS的发生可能是与环加氧酶(COX-2)过表达有关的一种炎性反应。化疗的中断和药物剂量的减少是最有效的治疗措施;一些预防治疗性药物,如维生素E、维生素B6和COX-2抑制剂有一定作用;中药在防治HFS方面值得期待。结论:HFS的防治研究取得了一定进展,对提高患者的生活质量及化疗效果有重要意义。     

Micro-RNA149 confers taxane resistance to malignant mesothelioma cells via regulation of P-glycoprotein expression

Multidrug resistance (MDR) represents a major hindrance to the efficacy of cancer chemotherapeutics. While surgical resection, radiation, and chemotherapy can be used to reduce tumor size, the subsequent appearance of drug resistant cells is a frequent problem. One of the main contributors to the development of MDR is increased expression of multi-drug resistant protein 1 (MDR1), also known as P-glycoprotein (P-gp). P-gp is a membrane-associated efflux pump that can efficiently remove internalized taxane-base chemotherapeutics thus preventing drug accumulation and maintaining cellular viability. Consequently, investigation into the molecular mechanisms responsible for regulation of P-gp expression is necessary to facilitate treatment of MDR tumors. Using molecular and biochemical approaches, we identified that the micro-RNA, miRNA149, contributes to the development of MDR within malignant mesothelioma cells by regulating the expression of MDR1.     

B超引导下穿刺注射化疗药物与无水乙醇联合治疗肝癌临床研究

为了探讨B超引导下穿刺注射化疗药物与无水乙醇联合治疗肝癌的可行性及疗效,对52例肝癌患者行B超引导下穿刺注射化疗药物与无水乙醇联合治疗,均给予2个周期治疗。结果示52例患者中CR8例,彩色超声显示瘤内无彩色血流,AFP降至正常,穿刺活组织检查无肿瘤细胞残留;PR20例,活组织检查有少量肿瘤细胞残留,但AFP降至正常;NC16例。初步研究结果提示,B超引导下穿刺注射化疗药物与无水乙醇联合治疗肝癌方法简便、安全、疗效满意,是一种较为理想的治疗方法。     

Autophagy and multidrug resistance in cancer

Multidrug resistance (MDR) occurs frequently after long-term chemotherapy,resulting in refractory cancer and tumor recurrence.Therefore,combatting MDR is an important issue.Autophagy,a self-degradative system,universally arises during the treatment of sensitive and MDR cancer.Autophagy can be a double-edged sword for MDR tumors:it participates in the development of MDR and protects cancer cells from chemotherapeutics but can also kill MDR cancer cells in which apoptosis pathways are inactive.Autophagy induced by anticancer drugs could also activate apoptosis signaling pathways in MDR cells,facilitating MDR reversal.Therefore,research on the regulation of autophagy to combat MDR is expanding and is becoming increasingly important.We summarize advanced studies of autophagy in MDR tumors,including the variable role of autophagy in MDR cancer cells.     

Relationship between the expression of cyclooxygenase 2 and MDR1/P-glycoprotein in invasive breast cancers and their prognostic significance

Introduction

Recent reports suggest that expression of the cyclooxygenase 2 (COX-2) enzyme may up-regulate expression of MDR1/P-glycoprotein (MDR1/P-gp), an exponent of resistance to cytostatic drugs. The present study aimed at examining the relationship between the expression of COX-2 and of MDR1/P-gp in a group of breast cancer cases.

Methods

Immunohistochemical reactions were performed using monoclonal antibodies against COX-2 and MDR1/P-gp on samples originating from 104 cases of primary invasive breast cancer.

Results

COX-2-positive cases were shown to demonstrate higher expression of MDR1/P-gp (P < 0.0001). The studies also demonstrate that COX-2 expression was typical for cases of a higher grade (P = 0.01), a shorter overall survival time (P < 0.0001) and a shorter progression-free time (P < 0.0001). In the case of MDR1/P-gp, its higher expression characterised cases of a higher grade (P < 0001), with lymph node involvement (P < 0001), and shorter overall survival (P < 0.0001) and progression-free time (P < 0.0001).

Conclusion

Our studies confirmed the unfavourable prognostic significance of COX-2 and MDR1/P-gp. We also document a relationship between COX-2 and MDR1/P-gp, which suggests that COX-2 inhibitors should be investigated in trials as a treatment supplementary to chemotherapy of breast cancers.     

Antimitotic chemotherapeutics promote adhesive responses in detached and circulating tumor cells

In the clinical treatment of breast cancer, antimitotic cytotoxic agents are one of the most commonly employed chemotherapies, owing largely to their antiproliferative effects on the growth and survival of adherent cells in studies that model primary tumor growth. Importantly, the manner in which these chemotherapeutics impact the metastatic process remains unclear. Furthermore, since dissemination of tumor cells through the systemic circulation and lymphatics necessitates periods of detached survival, it is equally important to consider how circulating tumor cells respond to such compounds. To address this question, we exposed both nontumorigenic and tumor-derived epithelial cell lines to two antitumor compounds, jasplakinolide and paclitaxel (Taxol), in a series of attached and detached states. We report here that jasplakinolide promoted the extension of microtubule-based projections and microtentacle protrusions in adherent and suspended cells, respectively. These protrusions were specifically enriched by upregulation of a stable post-translationally modified form of α-tubulin, and this occurred prior to, and independently of any reductions in cellular viability. Microtubule stabilization with Taxol significantly enhanced these effects. Additionally, Taxol promoted the attachment and spreading of suspended tumor cell populations on extracellular matrix. While the antiproliferative effects of these compounds are well recognized and clinically valuable, our findings that microfilament and microtubule binding chemotherapeutics rapidly increase the mechanisms that promote endothelial adhesion of circulating tumor cells warrant caution to avoid inadvertently enhancing metastatic potential, while targeting cell division.     

Decisive role of cyclooxygenase-2 and lipocalin-type prostaglandin D synthase in chemotherapeutics-induced apoptosis of human cervical carcinoma cells

The role of cyclooxygenase-2 (COX-2) in cancer remains controversial. Using cervical carcinoma cells (HeLa), the present study investigates the involvement of COX-2 in apoptosis elicited by the chemotherapeutics paclitaxel, cisplatin and 5-fluorouracil. Each compound led to a profound induction of COX-2 expression and prostaglandin (PG) synthesis, accompanied by a substantial decrease of viability and enhanced apoptosis. Cells were significantly less sensitive to apoptotic death when either COX-2 expression or its activity was suppressed by small-interfering RNA (siRNA) and by the selective COX-2 inhibitor NS-398, respectively. Experiments performed to clarify how COX-2 leads to apoptosis revealed a profound proapoptotic action of PGD2 and its dehydration product, 15-deoxy-Delta(12,14) PGJ2 (15d-PGJ2). In line with these findings, chemotherapeutics-induced apoptosis was prevented by siRNA targeting lipocalin-type PGD synthase (L-PGDS), which catalyses the isomerization of PGH(2) to PGD2. Moreover, apoptosis by chemotherapeutics, PGD2 and 15d-PGJ2 was suppressed by the peroxisome proliferator-activated receptor gamma (PPARgamma) antagonist, GW-9662 or PPARgamma siRNA. Finally, a COX-2-dependent apoptotic mechanism of all investigated chemotherapeutics was confirmed in human lung cancer cells (A549) as well as in another cervical carcinoma cell line (C33A). Collectively, this study suggests COX-2 induction and synthesis of L-PGDS-derived, PPARgamma-activating PGs as a decisive target by which several chemotherapeutics induce apoptosis. COX-2 is therefore suspected to sensitize cancer cells to apoptotic death under certain circumstances, suggesting that COX-2 inhibition during cancer therapy could diminish its efficacy.     

Potentiation of chemotherapeutics by the Hsp90 antagonist geldanamycin requires a steady serum condition

Inhibition of Hsp90 potentiates diverse chemotherapeutics, but it is not clear if this applies only to specific agents, tumor types or conditions. The aim of this report is to determine the effect of serum starvation (SS) on potentiation. SUIT2 cells were cultured with and without the presence of serum and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays were carried out at time intervals. Cytotoxic agents were added individually or in combination. Immunohistochemistry of tumor samples and immunofluorescence of cultured cells were used to examine Hsp90 localization. In the presence of serum an at least additive effect of combining the Hsp90 inhibitor geldanamycin (GA) with 5-fluorouracil (5FU) was demonstrated. Following pretreatment with GA, 5FU and GA were synergistic. However, during SS GA was protective against 5FU. Geldanamycin also protected cells from 12-O-tetradecanoylphorbol-13-acetate (TPA) during SS. Protection of cells is transitory, as after 24 h of SS GA again has an at least additive negative effect on vitality with 5FU or TPA. Serum starvation of pancreatic cancer cell lines causes normally largely cytoplasmic Hsp90 to become predominantly nuclear localized. Hsp90 nuclear localization was observed in pancreatic and prostate tumors. Hsp90 binding to a pro-apoptotic client could explain the transitory protection of cells by Hsp90 inhibition during SS. Although potentiation of chemotherapeutics by Hsp90 inhibition is probably a general phenomenon, design of clinical trials should take into account that continuous co-administration may be ineffective because of a balance of synergy of the drugs in some cells and mutual inhibition of the two drug activities in other cells.     

Bacterially derived 400 nm particles for encapsulation and cancer cell targeting of chemotherapeutics

Systemic administration of chemotherapeutic agents results in indiscriminate drug distribution and severe toxicity. Here we report a technology potentially overcoming these shortcomings through encapsulation and cancer cell-specific targeting of chemotherapeutics in bacterially derived 400 nm minicells. We discovered that minicells can be packaged with therapeutically significant concentrations of chemotherapeutics of differing charge, hydrophobicity, and solubility. Targeting of minicells via bispecific antibodies to receptors on cancer cell membranes results in endocytosis, intracellular degradation, and drug release. This affects highly significant tumor growth inhibition and regression in mouse xenografts and case studies of lymphoma in dogs despite administration of minute amounts of drug and antibody; a factor critical for limiting systemic toxicity that should allow the use of complex regimens of combination chemotherapy.